Chronic enalapril treatment increases transient outward potassium current in cardiomyocytes isolated from right ventricle of spontaneously hypertensive rats

作者：Rodrigues Junior Luiz Fernando; de Azevedo Carvalho Ana Carolina; Pimentel Enildo Broetto; Mill Jose Geraldo; Matheus Nascimento Jose Hamilton

来源：Naunyn-Schmiedeberg's Archives of Pharmacology, 2017, 390(3): 225-234.

DOI：10.1007/s00210-016-1322-7

• Angiotensin-converting enzyme inhibitors
• Enalapril
• Hypertension
• Hypertrophy
• SHR
• Transient outward potassium current

It has been well established that chronic pressure overload resulting from hypertension leads to ventricular hypertrophy and electrophysiological remodeling. The transient outward potassium current (I (to)) reduction described in hypertensive animals delays ventricular repolarization, leading to complex ventricular arrhythmias and sudden death. Antihypertensive drugs, as angiotensin-converting enzyme inhibitors (ACEi), can restore I (to) and reduce the incidence of arrhythmic events. The purpose of this study was to evaluate the differential effects of long-term treatment with ACEi or direct-acting smooth muscle relaxant on the I (to) of left and right ventricle myocytes of spontaneously hypertensive rats (SHR). Animals were divided into four groups: normotensive Wistar-Kyoto rats (WKY), hypertensive (SHR), SHR treated for 6 weeks with enalapril 10 mg/kg/day (SHRE), or hydralazine 20 mg/kg/day (SHRH). Systolic blood pressure (SBP) and hypertrophy index (heart weight/body weight (HW/BW)) were determined at the end of treatment period. Cell membrane capacitance (C (m)) and I (to) were assessed in cardiomyocytes isolated from left and right ventricles. The SHR exhibited significantly increased SBP and HW/BW when compared to the WKY. The treated groups, SHRE and SHRH, restored normal SBP but not HW/BW. The SHR group exhibited a diminished I (to) in the left but not the right ventricle. Both the treated groups restored I (to) in the left ventricle. However, in the right ventricle, only enalapril treatment modified I (to). The SHRE group exhibited a significant increase in I (to) compared to all the other groups. These findings suggest that enalapril may increase I (to) by a pressure overload independent mechanism.

• 出版日期2017-3